Hydroxycarbamide for patients with silent cerebral infarcts: outcomes and patient preference

Rushton, Tullia; Aban, Inmaculada; Young, Daniel W.; Howard, Thomas H.; Hilliard, Lee; Lebensburger, Jeffrey D.

doi:10.1111/bjh.14526

Cited by 8 publications

(9 citation statements)

References 17 publications

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“…The impact of hydroxyurea on silent infarct occurrence or recurrence has not been tested in randomized trials. While the improvement of anemia on hydroxyurea could suggest some silent infarct prevention, several observational studies have reported a persistant incidence of silent infarct on hydroxyurea therapy [91,92].…”

Section: Who To Consider For Allogeneic Stem Cell Transplantation mentioning

confidence: 99%

Why, Who, When, and How? Rationale for Considering Allogeneic Stem Cell Transplantation in Children with Sickle Cell Disease

Bernaudin

2019

JCM

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Considering the progress made in the management of sickle cell disease during the past 30 years, along with the excellent results obtained with hematopoietic stem cell transplantation (SCT), it is important to reexamine why, who, when and how to recommend allogeneic SCT in children with sickle cell disease. While sickle cell disease has a low risk of death in children and a high risk for morbidity during aging, SCT carries an early risk of death, graft-vs-host disease and infertility. Nevertheless, SCT offers at least 95% chance of cure with low risk of chronic graft-vs-host disease when a matched-sibling donor is available and the risks of infertility can be reduced by ovarian, sperm or testis cryopreservation. Thus, all available therapies such as hydroxyurea, transfusions and SCT should be presented to the parents, providers, and affected children and discussed with them from infancy. Furthermore, the use of these therapies should be adjusted to the severity of the disease and to local availabilities in order to choose the treatment offering the best benefit/risk ratio.

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Section: Who To Consider For Allogeneic Stem Cell Transplantation mentioning

confidence: 99%

Why, Who, When, and How? Rationale for Considering Allogeneic Stem Cell Transplantation in Children with Sickle Cell Disease

Bernaudin

2019

JCM

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“…25 Similarly for SCIs, data suggest a likely benefit of HU in prevention of SCIs; however, a lack of randomized controlled trials leaves the exact role and degree of benefit of HU unclear. [26][27][28] Both HU and CTT increase arterial oxygen content (CaO 2 ), which is low in SCA, via an increase in Hb. The cerebral metabolic rate of oxygen use (CMRO 2 ), a measure of oxygen demand within the brain, is the product of CaO 2 , cerebral blood flow (CBF) and oxygen extraction fraction (OEF).…”

Section: Introductionmentioning

confidence: 99%

Hydroxyurea reduces cerebral metabolic stress in patients with sickle cell anemia

Fields¹,

Guilliams

Ragan

et al. 2019

Blood

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Chronic transfusion therapy (CTT) prevents stroke in selected patients with sickle cell anemia (SCA). We have shown that CTT mitigates signatures of cerebral metabolic stress, reflected by elevated oxygen extraction fraction (OEF), which likely drives stroke risk reduction. The region of highest OEF falls within the border zone, where cerebral blood flow (CBF) nadirs; OEF in this region was reduced after CTT. The neuroprotective efficacy of hydroxyurea (HU) remains unclear. To test our hypothesis that patients receiving HU therapy have lower cerebral metabolic stress compared with patients not receiving disease-modifying therapy, we prospectively obtained brain magnetic resonance imaging scans with voxel-wise measurements of CBF and OEF in 84 participants with SCA who were grouped by therapy: no disease-modifying therapy, HU, or CTT. There was no difference in whole-brain CBF among the 3 cohorts (P = .148). However, whole-brain OEF was significantly different (P < .001): participants without disease-modifying therapy had the highest OEF (median 42.9% [interquartile range (IQR) 39.1%-49.1%]), followed by HU treatment (median 40.7% [IQR 34.9%-43.6%]), whereas CTT treatment had the lowest values (median 35.3% [IQR 32.2%-38.9%]). Moreover, the percentage of white matter at highest risk for ischemia, defined by OEF greater than 40% and 42.5%, was lower in the HU cohort compared with the untreated cohort (P = .025 and P = .034 respectively), but higher compared with the CTT cohort (P = .018 and P = .029 respectively). We conclude that HU may offer neuroprotection by mitigating cerebral metabolic stress in patients with SCA, but not to the same degree as CTT.

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“…An increase in hemoglobin concentration improves cerebral arterial oxygen content, which is associated with decreased cerebral metabolic stress in patients receiving hydroxyurea compared to those without disease‐modifying therapy 9 . In addition, hydroxyurea has been associated with normalization of elevated cerebral blood flow velocities noted on TCD screening 10‐12 . Thus, the resultant increased cerebral arterial oxygen content and normalization of blood flow induced by hydroxyurea allow for better matching of oxygen supply and cerebral metabolic demand, which could also decrease risk of infarction.…”

Section: Discussionmentioning

confidence: 99%

“…Cumulative damage to cerebral tissue is inevitable for most patients with SCA who do not receive disease‐modifying therapy 5 . Hydroxyurea is the most established and effective disease‐modifying pharmacotherapy for SCA and is neuroprotective 6‐11 . In addition, hydroxyurea improves peripheral oxygen saturation, 12 which correlates with cerebral oxygen saturation in patients with SCA 3 .…”

Section: Introductionmentioning

confidence: 99%

Hydroyxurea improves cerebral oxygen saturation in children with sickle cell anemia

et al. 2021

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Neurologic complications are common in patients with sickle cell anemia (SCA), but conventional tools such as MRI and transcranial Doppler ultrasonography (TCD) do not fully assess cerebrovascular pathology. Cerebral tissue oximetry measures mixed oxygen saturation in the frontal lobes (SCTO2) and provides early prognostic information about tissue at risk of ischemic injury. Untreated patients with SCA have significantly lower SCTO2 than healthy controls that declines with age. Hydroxyurea is effective in preventing many SCA‐related complications, but the degree to which it preserves normal neurophysiology is unclear. We analyzed participants enrolled in the Therapeutic Response Evaluation and Adherence Trial (TREAT, NCT02286154), which enrolled participants initiating hydroxyurea using individualized dosing (new cohort) and those previously taking hydroxyurea (old cohort) and was designed to monitor the long‐term benefits of hydroxyurea. Cerebral oximetry was performed at baseline and annually. For the new cohort (median starting age = 12 months, n = 55), mean baseline SCTO2 was normal before starting hydroxyurea (mean 65%, 95% CI 58–72%) and significantly increased after 2 years (mean 72%, 95% CI 65–79%, p < .001). The SCTO2 for patients receiving long‐term hydroxyurea (median age = 9.6 years) was normal at study entry (mean 66%, 95% CI 58–74%) and remained stable across 2 years. Both cohorts had significantly higher SCTO2 than published data from predominantly untreated SCA patients. Cerebral oximetry is a non‐invasive method to assess cerebrovascular pathology that complements conventional imaging. Our results indicate that hydroxyurea suggests protection against neurophysiologic changes seen in untreated SCA.

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Hydroxycarbamide for patients with silent cerebral infarcts: outcomes and patient preference

Cited by 8 publications

References 17 publications

Why, Who, When, and How? Rationale for Considering Allogeneic Stem Cell Transplantation in Children with Sickle Cell Disease

Why, Who, When, and How? Rationale for Considering Allogeneic Stem Cell Transplantation in Children with Sickle Cell Disease

Hydroxyurea reduces cerebral metabolic stress in patients with sickle cell anemia

Hydroyxurea improves cerebral oxygen saturation in children with sickle cell anemia

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